Mild Symptoms of SARS-CoV-2 Infection in a 3-Days-Old Newborn with Congenital Heart Disease: A Case Report

Background: SARS-CoV-2 as a member of Coronavirus family, caused a global pandemic in late 2019 and raised concerns about its morbidity and mortality among immune-deficient individuals. Till now, several pediatric cases infected with SARS-CoV-2 have been reported, and some have noted susceptibility to infection in infants and young children, especially those with congenital comorbidities. In this report, we discuss the clinical course, administered treatments, and outcomes of SARS-COV-2 infection in an infant suffering from cardiovascular comorbidity. Case Presentation: We describe a newborn referred to hospital 72 hours postpartum, diagnosed with pulmonary atresia with ventricular septal defect (PA-VSD), and subsequently found to be infected with the SARS-COV-2 virus. The patient presented with tachypnea, lethargy, and a history of recent fever and myalgia in his father. He received intravenous fluid and antibiotic therapy based on an established protocol for COVID-19 treatment by Iran health ministry and was discharged after five days of hospitalization without further complications. Two weeks after discharge, he was referred to the cardiac surgery department for surgical treatment after obtaining a negative result for nasopharyngeal sample SARS-CoV-2 RT-PCR. Conclusions: Mild symptoms and no need for excessive oxygen supports in the current case demonstrate pediatrics patients with COVID-19 have a better prognosis and fewer complications compared with adults, even at early childhood and with the presence of serious cardiac complications.

Obacunone Attenuates Liver Fibrosis with Enhancing Anti-Oxidant Effects of GPx-4 and Inhibition of EMT

Obacunone, a limonin triterpenoid extracted from Phellodendronchinense Schneid or Dictamnus dasycarpusb Turcz plant, elicits a variety of pharmacological effects such as anti-inflammatory, anti-neoplastic, anti-oxidation, and anti-lung-fibrosis ones. However, the anti-fibrotic effect of obacunone and the detailed underlying mechanism in liver fibrosis remain unclear. Liver fibrosis is a debilitating disease threatening human health. Transforming growth factor (TGF)-β/P-Smad is a major pathway of fibrosis featured with epithelia mesenchymal transformations (EMT) and collagen depositions, accompanying with excessive oxygen-free radicals. Nrf-2 acts as a key anti-oxidative regulator driving the expressions of various antioxidant-related genes. Glutathionperoxidase-4 (GPx-4) is a member of the glutathione peroxidase family that directly inhibits phospholipid oxidation to alleviate oxidative stress. In the present study, we aimed to explore the role of obacunone in mouse liver fibrosis model induced by carbon tetrachloride (CCl4) and in hepatic stellate cells (LX2 cell line) challenging with TGF-β. Obacunone demonstrated potent ameliorative effects on liver fibrosis both in activated LX2 and in mice liver tissues with reduced levels of α-SMA, collagen1, and vimentin. Obacunone also remarkably suppressed the TGF-β/P-Smad signals and EMT process. Meanwhile, obacunone exerted a potent anti-oxidation effect by reducing the levels of reactive oxygen species (ROS) in both models. The antioxidant effect of obacunone was attributed to the activation of GPx-4 and Nrf-2. In addition, the therapeutic effect of obacunone on LX2 cells was significantly removed in vitro plus with GPx-4 antagonist RSL3, in parallel with the re-elevated levels of ROS. Thus, we demonstrate that obacunone is able to attenuate liver fibrosis via enhancing GPx-4 signal and inhibition of the TGF-β/P-Smad pathway and EMT process.

Hypoxia Regulation of ndrgs

ABSTRACTMany organisms rely on oxygen to generate energy in the form of adenosine triphosphate (ATP). During severe hypoxia, the production of ATP decreases due to diminished activity of the electron transport chain, leading to cell damage or death. Conversely, excessive oxygen causes oxidative stress that is equally damaging to cells. To mitigate pathological outcomes, organisms have evolved mechanisms to adapt to fluctuations in oxygen levels. Zebrafish embryos are remarkably hypoxia-tolerant, surviving anoxia (zero oxygen) for hours in a hypometabolic, energy-conserving state. To begin to unravel underlying mechanisms, we analyze here the distribution and hypoxia-dependent regulation of members of the N-myc Downstream Regulated Gene (Ndrg) family, Ndrg 1-4. These genes have primarily been studied in cancer cells, and hence little is understood about their normal function. We show here using in situ hybridization that, under normoxic conditions, ndrgs are expressed in metabolically-demanding organs of the zebrafish embryo, such as the brain, kidney, and heart. Following exposure of embryos to different severity and durations of hypoxia, we observed that ndrgs are differentially regulated and that ndrg1a is the most responsive member of this family, with nine-fold upregulation following prolonged anoxia. We further show that this treatment resulted in de novo expression of ndrg1a in tissues where it is not observed under normoxia, such as head vasculature, the inner ear, and somites. These findings provide an entry point into understanding the role of this conserved gene family in hypoxia adaptation of normal cells.

Effect of Transcriptional Regulatory Factor FoxO3a on Central Nervous System Oxygen Toxicity

Central nervous system (CNS) oxygen toxicity (CNS-OT) is a toxic reaction that appears after the inhalation of gas at an excessive oxygen partial pressure during underwater operation or hyperbaric oxygen (HBO) treatment. The mechanism of CNS-OT has not been clearly characterized. Though it has been attributed to the excessive oxidative stress induced by HBO, evidences against this hypothesis have been reported. Here we find that Forkhead box protein O3 (FoxO3a) is important for CNS-OT protection. FoxO3a knock-out (KO) mice had a shorter latency to develop convulsions and greater number of seizures within a certain period of time. The acute lung injury (ALI) induced by CNS-OT was also more severe in FoxO3a KO mice. Further analysis reveals a significant decrease in the activity of catalase (CAT), an antioxidant enzyme and a significant increase in the content of malondialdehyde (MDA), an oxidative product, in brain tissues of FoxO3a KO mice. Short-time HBO exposure could increase FoxO3a expression level and trigger its nuclear translocation. The level of nuclear localized FoxO3a peaked at 8 h after exposure. Our results demonstrate that the activity of FoxO3a is highly sensitive to HBO exposure and FoxO3a plays important roles in protecting CNS-OT. Further mechanic analysis reveals that FoxO3a protects CNS-OT via activating antioxidative signaling pathway.

Biological effects of the oxygen molecule in critically ill patients

The medical use of oxygen has been widely and frequently proposed for patients, especially those under critical care; however, its benefit and drawbacks remain controversial for certain conditions. The induction of oxygen therapy is commonly considered for either treating or preventing hypoxia. Therefore, the concept of different types of hypoxia should be understood, particularly in terms of their mechanism, as the effect of oxygen therapy principally varies by the physiological characteristics of hypoxia. Oxygen molecules must be constantly delivered to all cells throughout the human body and utilized effectively in the process of mitochondrial oxidative phosphorylation, which is necessary for generating energy through the formation of adenosine triphosphate. If the oxygen availability at the cellular level is inadequate for sustaining the metabolism, the condition of hypoxia which is characterized as heterogeneity in tissue oxygen tension may develop, which is called dysoxia, a more physiological concept that is related to hypoxia. In such hypoxic patients, repetitive measurements of the lactate level in blood are generally recommended in order to select the adequate therapeutic strategy targeting a reduction in lactate production. Excessive oxygen, however, may actually induce a hyperoxic condition which thus can lead to harmful oxidative stress by increasing the production of reactive oxygen species, possibly resulting in cellular dysfunction or death. In contrast, the human body has several oxygen-sensing mechanisms for preventing both hypoxia and hyperoxia that are employed to ensure a proper balance between the oxygen supply and demand and prevent organs and cells from suffering hyperoxia-induced oxidative stress. Thus, while the concept of hyperoxia is known to have possible adverse effects on the lung, the heart, the brain, or other organs in various pathological conditions of critically ill patients, and no obvious evidence has yet been proposed to totally support liberal oxygen supplementation in any subset of critically ill patients, relatively conservative oxygen therapy with cautious monitoring appears to be safe and may improve the outcome by preventing harmful oxidative stress resulting from excessive oxygen administration. Given the biological effects of oxygen molecules, although the optimal target levels remain controversial, unnecessary oxygen administration should be avoided, and exposure to hyperoxemia should be minimized in critically ill patients.

Micro-Oxygenation in Upflow Anaerobic Sludge Bed (UASB) Reactors Using a Silicon Membrane for Sulfide Oxidation

Sulfide produced by sulphate-reducing bacteria in anaerobic reactors can seriously affect biogas quality. Microaeration has become a reliable way to remove sulfide, by promoting its oxidation. However, limited research is available regarding its application in upflow anaerobic sludge bed (UASB) reactors. In this research, silicon membranes were studied as a mechanism to dose oxygen in USAB reactors. Two configurations were tested: the membrane placed inside the reactor or in an external module. Our results show that the external membrane proved to be a more practical alternative, providing conditions for sulfide oxidation. This led to a reduction in its concentration in the liquid effluent and biogas. External membrane configuration achieved a sulfide conversion rate of 2.4 g-S m2 d−1. Since the membrane was not sulfide-selective, methane losses were observed (about 9%). In addition, excessive oxygen consumption was observed, compared to the stoichiometric requirement. As is the case for many membrane-based systems, membrane area is a key factor determining the correct operation of the system.